SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW CYCLOPENTENO[B]THIOPHENE DERIVATIVES AS LOCAL-ANESTHETIC AND ANTIARRHYTHMIC AGENTS

A series of ethyl 2-subsituted amino-cyclopenteno[b]thiophen-3-carboxy lates was synthesized as a carticaine analogues and evaluated for thei r local anesthetic and antiarrhythmic activity. Compounds ethyl 2-[1-o xo-2-(ethylamino)ethylamino]-(4a), ethyl 2-[1-oxo-2-(n-propylamino)-et hylamino]-(4c), ethyl 2-[1-oxo-2-(4-methylpiperazino)ethylamino]-(4e), ethyl 2-[1-oxo-2-(ethylamino)propylamino]-(5a) and ethyl )propylamino ]cyclopenteno[b]thiophen-3-carboxylate (5c) proved to possess local an esthetic and antiarrhythmic activity comparable to carticaine and lido caine, The active compounds exert their antiarrhythmic potency via blo cking Na+ channels as in case of 5c or blocking Ca+2 channels as in ca se of 4a, 4e and 5c. Compound 4e exhibited a dual mechanism by blockin g both Na+ and Ca+2 channels.